2840
J. Org. Chem. 1985,50, 2840-2841
tution of phenyl for H Figure 3, dotted line), nor is it supported by the lack of analogous effects of phenyl-formethyl substitution in di0~etanes.l~The latter case however is complicated by postulated reverse reactions, and the symmetry of alkoxy radicals may lessen the geometrical demands for homoconjugation with the aromatic ring. More definitive evidence on this matter would come from electron detachment studies of substituted benzyl alcoholate ions, but these do not appear to have been carried out. Acknowledgment. This work has been supported by a fellowship to E.M.Q. from the 3M Company. (13)(a) Richardson, W. H.; Anderegg,J. H.; Price, M. E.; Tappen, W. A,; ONeal, H. E. J. Org. Chem. 1978,43,2236-2241.(b) Richardson, W. H.; Yelvington, M. B.; ONeal, H. E. J . Am. Chem. SOC.1972, 94, 1619-1623.
Registry No. (CH3)2CHCH21,513-38-2; p-FC6H4CHC1CH3, 456-16-6; p-C1C6H4CHClCH3,20001-65-4; p-BrC6H4CHC1CH3, 20488-10-2;p-CH30C6H4CHClCH3, 1538-89-2; Ph2CHBr,776-74-9; trans-C6H5CH(CH3)ON=NOCH(CH3)C6H5, 97012-02-7; transC6HSCD(CH3)0N=NOCD(CH3)C6H5, 97012-03-8; trans-cC6HlION=NOC6H11-c, 86886-18-2; trans-C6H,CH20N= NOCH2C6H5,86886-20-6;trans-CH30N=NOCH3, 86886-15-9; trans-CH3CH20N=NOCH2CH3, 91606-80-3; t r a n s (CH3)2CHON=NOCH(CH3)2, 86886-16-0; trans(CH3)2CHCH20N=NOCH2CH(CH3)2, 97012-04-9; trans-pFC6H&H(CH3)0N=NOCH(CH3)C,H,-p-F, 97012-05-0; transp-CIC6H4CH(CH3)ON=NOCH(CH3)CsH,-p-C1, 97012-06-1; trans-p-BrC6H4CH(CH3)ON=NOCH(CH3)C6H4-p-Br, 9701207-2; trans-p-CH30C6H4CH(CH3)ON=NOCH(CH3)C6H4-pOCH,, 97012-08-3; ~ ~ u ~ ~ - ( C ~ H ~ ) ~ C H O N = N O 97012CH(C~H~)~, 10-7; p-FC6H4COCH3, 403-42-9; p-CIC6H4COCH3, 99-91-2; p BrC6H4COCH3, 99-90-1; p-CH30C6H,COCH3, 100-06-1; pCH30C6H4CH(OH)CH3,3319-15-1;1-tetralol, 529-33-9; 1-tetralyl chloride, 58485-68-0;trans-bis(1-tetralyl)hyponitrite,97012-09-4.
Reactions of the Chlorine Complex of Tetrahydrothiophene Donald L. Schmidt,* Jerry P. Heeschen, Thomas C. Klingler, and Leslie P. McCarty The Dow Chemical Company, Midland, Michigan 48640
Received May 24, 1984 The chlorine complex of tetrahydrothiophene (THT) undergoes the Pummerer reaction to yield not only the expected 2-chloro- and 2,3-dichlorotetrahydrothiopheneproducts but also 1-(2-chlorotetrahydro-3-thienyl)tetrahydrothiophenium chloride (lo), which upon hydrolysis yields l-(tetrahydro-2-hydroxy-3-thienyl)tetrahydrothiophenium chloride 3 and upon elimination of HCl produces 1-(4,5-dihydro-3-thienyl)tetrahydrothiophenium chloride (2). The sulfonium 10 waa formed by the addition of the chlorine-THT complex to the Pummerer-derived 2,3-dihydrothiophene. The sulfonium formation was monitored in CC14,CH2C12,and liquid SO2 by proton NMR, and the addition of the complex to cyclohexene, dihydrofuran, styrene, and thiophene was studied. There was a dramatic increase in reactivity of the complex in sulfur dioxide both to addition and substitution type reactions.
Aryl cyclic sulfonium zwitterions are polymerizable m~nomersl-~ that are prepared4by the reaction of a phenol with the 1:l complex of chlorine and tetrahydrothiophene 1. The electrophilic substitution to yield sulfonium goes exclusively para to the phenolic hydroxy. If the para position is blocked, then ortho substitution occurs a t a much lower rate. It is interesting that liquid SO2 is the only solvent that gives a practical reaction rate for ortho substitution to phenol^.^
The chlorosulfonium salt 1 may be formed by chlorination of tetrahydrothiophene (THT) with chlorine or sulfuryl chloride or from tetrahydrothiophene 1-oxide (THTO) in cold, saturated HC1 solutions of methanol2 or water-methan01.~ In the course of preparing large quantities of the zwitterion, we observed that excess 1 and elevated reaction temperatures produced toxic solutions. The toxicity was
not related to the T H T substitution reaction to phenols but was a result of the unexpected addition of 1 to the Pummerer-derived 2,3-dihydrothiopheneto yield bioactive sulfoniums. We report here a subsequent study of the Pummerer rearrangements of 1 and a previously unreported reaction of 1 with alkenes. Isolation of Sulfoniums. The zwitterion solutions containing the toxic substances were analyzed by highperformance liquid chromatography (HPLC) using a cationic exchange column for separation of the unknown species. Because neuromuscular blockade was the pharmacological property related to toxicity, a bioassay technique reported by KordaEi6was used to monitor the HPLC. This method proved both sensitive and semiquantitative. Sufficient material was isolated from the most bioactive HPLC peak for partial characterization. A sample of crystalline material was isolated by picrate precipitation from a solution of zwitterion containing the toxic substance. The chloride salt of this material was identical by bioassay and proton NMR with samples isolated by HPLC. On the bases of NMR, IR, elemental, and mass spectral analyses this bioactive compound was tentatively assigned structure 2. Later, chemical considerations confirmed p(3)
(1)Hatch, M.J.;Yoshimine, M.; Schmidt, D. L.; Smith H. B. J.Am. Chem. SOC.1971,93,4617. (2)Schmidt, D. L.; Smith, H. B.; Yoshimine, M.; Hatch, M. J. J. Polym. Sci., A-I 1972,IO, 2951. (3)Schmidt, D. L. In ‘Ring-opening Polymerization”; Saequsa, T., Goethals, E., Eds.: American Chemical Society: Washington, DC; 1977: ACS Symposium Series, pp 318. (4)Klingler, T. C.;Schmidt, D. L.; Jensen, W., Jr.; Urchick, D. U S . Patent 4089877,1978. ( 5 ) Schmidt, D. L., unpublished results.
(6)Kordai, M. Int. J. Neuropharmacol. 1964,3, 77. The bioassay depended upon the percent depression of an isolated perfused rat phrenic nerve-diaphram (IPD) as described by KordaH. The toxicity was due to neuromuscular blockage and the potency was quantitated by the percent depression in the contraction of the nerve-diaphragm. After the compounds had been isolated, the potency was compared by the quantity needed for a 25% depression. The LD, in mice was determined by intraperitoneal administration and the measured LD, values were 2a, 0.83 mg/kg; 3a, 3.16 mg/kg; and 48,6.81mg/kg.
zwitterion monomer
0022-326318511950-2840%01.50/0 D 1985 American Chemical Societv
Chlorine Complex of Tetrahydrothiophene
J. Org. Chem., Vol. 50, No. 16, 1985 2841
n
2a. XsCI2 b. X 9 picrate
THT+ substitution. When 2a was heated, ring-opening occured by chloride attack at a ring carbon a to the sulfonium to yield the nonionic species 2R. While obtaining larger quantities of 2, by decomposition of 1 in SO2, minor product 3 was isolated by fractional
n
3a, X = C I 3b, X = picrate
crystallization, which had a retention time that matched a bioactive HPLC peak obtained from the original zwitterion solutions. When 1 was decomposed in CH2C12,3 became the major product; however, warming appeared to convert 3 to 2. Since NMR indicated that CHOH methine proton of 3 is vicinal to only one other proton, the hydroxyl was assigned to be in the 4 2 ) position. Small amounts of a third sulfonium (4) were obtained when 1 was decomposed in SOz followed by addition of water and then allowed to stand at 25 "C. This structure
n
4a, X = C I 4b,X = picrate
was confirmed by comparison of the mass spectrum and NMR of the isolated material with the authentic compound. The authentic compound was prepared by displacement of the benzenesulfonate ester of 3-hydroxytetrahydrothiophene with THT. The sulfonium 4 was not detected by HPLC in any of the zwitterion solutions which contained toxic substance. Decomposition Studies in C C 4 , CH2C12,and SOz. The decomposition of 1 in CC14 gave two phases: a top semisolid, water-soluble phase and a bottom CC14phase. The CC14 phase contained 2-chlorotetrahydrothiophene (2-C1-THT 5) and cis- and trans-2,3-dichlorotetrahydrothiophene (2,3-diCl-THT, 6 ) in a 5 / 6 ratio of 0.4. The cis isomer has not been reported previously. Addition of D20 appeared to hydrolyze 6 to 2-hydroxy-3-chlorotetrahydrothiophene ( 7 ) and 5 to 2-hydroxytetrahydrothiophene (8). Addition of D20to the water-soluble phase gave 2 and 3 and THTO from hydrolysis of 1. When the decomposition of 1 was carried out in CH2Clz and the solution was extracted with cold D20, 3 was observed but little 2 was detected. When the D20 solution was warmed, 2 became the main product, suggesting that both 2 and 3 came from the same precursor. The decomposition of 1 in SO2 was studied by taking D20-quenchedsamples. After 1h, NMR analysis indicated a species consistent with a-(sulfonic acid)-p-THT+ substituted THT 9. After 3 h, the amount of 9 had increased and 2 began to appear. Upon elimination of most of the SO2 before quenching no 9 could be detected; however, both 3 and 2 were observed. Apparently the formation of
the sulfonic acid 9 requires the presence of a strong H2S03 solution. It appears that 9,3, and 2 were derived from the same precursor. Finally, the decomposition of 1 in SO2 was monitored in a sealed NMR tube at -15 OC. The complex 1 was detected initially and slowly decreased with time. After about 6 h, NMR absorptions were detected that were consistent with the cis and trans isomers of the a-chloro p-sulfonium substituted THT structure 10. Soon after the appearance of 10,2 was detected and continued to increase during the decomposition. Mechanism. NMR studies were performed on HC1 solutions of 3 to both determine if 3 could be converted to 10 and to establish chemical shifts of 10. Adding concentrated HC1 to an aqueous solution of 3 produced a weak absorption at 6.18 ppm which was assigned tentatively as the a proton of 10. The main effect of saturating this solution with HC1 gas was the conversion of 3 to 2. Addition of HC1 gas to a methanol solution of 3 at 0 OC caused the complete loss of 3 and the appearance of 10 and the a-methoxy derivative 11. Both 10 and 11 appeared as major/minor sets of absorptions in methanol-HC1. The predominate isomer of 10 in methanol-HC1 had coupled a and p proton absorptions at 6.28 (4.2 Hz) and 4.43 ppm, and the lesser isomer at 6.26 and 4.60 ppm. The major isomer of 11 in methanol-HC1 had Q and p proton absorptions at 5.41 (d, 4.3 Hz) and 4.19 ppm and a methoxy singlet at 3.30 ppm. The minor isomer of 11 had an a proton absorption at 5.54 ppm but the @ proton shift was not established. Since it was established that 3 has the hydroxyl on the a position and can be converted to 10, it follows that 10 must have the chlorine on the Q position. Similarly, since 3 can be converted to 2, then 2 must also have the sulfonium in the p position. From the data available, it appears that the generation of the sulfoniums 10 and 2 is consistent with the mechanism suggested by Wilson and AlberL7ys These workers proposed the intermediacy of a sulfocarbonium ion 12 (Scheme I) which either eliminates HC1 to yield 2,3-dihydrothiophene (13) or is attacked by chloride to yield 2-C1-THT (5). Chlorination of 13 produces 2,3-diCl-THT ( 6 ) . A plausible mechanism for formation of 10 is the addition of the chlorosulfonium salt 1 to 13 to yield 10. Elimination of HC1 from 10 would produce 2 (Scheme I). This is consistent with our observations that 3 is mainly (7) Wilson, G. E., Jr.; Albert, R. J. Org. Chem. 1973, 38,2156. (8) Wilson, G. E., Jr.; Albert, R. J. Org. Chem. 1973, 38,2160.
2842 J. Org. Chem., Vol. 50, No. 16, 1985
isolated from low-temperature decomposition conditions and 2 is the major product at higher temperatures. We observed that when 2,3-dihydrothiophene (13) was added to a fresh SO2 solution of 1, a 2% yield of 2b was isolated, but under identical conditions in the absence of 13 no 2b could be isolated. Similar results were obtained by using a CH2C12solvent except less sulfonium was obtained. These observations are in agreement with the reaction of 1 with the alkene intermediate 13. The isolation of small amounts of the sulfonium 4 from the decomposition of 1 in SO2-HC1-H20 also suggests the intermediacy of 2,3-dihydrothiophene (13). It is known that sulfides in strong aqueous acids react with alkenes to yield sulfoniums.10 Thus THT could react under the proper conditions with 13 to yield 4, although the 4 2 ) sulfonium would be expected to be the favored product. We were unable to prepare 4 under the conditions used by the addition of T H T to 13 in acid but obtained only polymer. The conversion of 4 to 10 by the Pummerer reaction using chlorine in CH2C12or SO2 was also unsuccessful. Because of the known reactivity of a-chloro sulfides, it is not surprising that 10 is easily converted either to the a-hydroxy 3 by water or to the a-sulfonic acid 9 by concentrated sulfurous acid. Similarly, 3 reacts with either concentrated HC1 to yield 10 or with HC1-CH30H to give the methoxy derivative 11. We found small amounts of cis-2,3-diCl-THT in the reaction mixture, whereas Wilson and Albert8 detected only the trans isomer on the basis of isolation of the methoxy derivatives. Apparently the ratio of the 2-C1T H T to 2,3-diC1 T H T that we measured by NMR also differs from reported values based on conversion to the methoxy derivatives8or post addition of trimeth~lamine.~ It appears that the electrophilic addition of 1 to 13 to yield 10 is in competition with the chlorination of 13. It has also been shown' that HCl reacts with 13 to give 5. Considering these competitive reactions, the reaction of 1 with 13 is probably quite fast. On the basis of decomposition studies, it was difficult to determine if the addition of 1to 13 was solvent-sensitive. It appears, however, that the dehydrochlorinationof 10 to form 2 is solvent-sensitive and this reaction is much slower in CC14and CH2Clthan in SO2. Reaction with Alkenes. The reactivity of the chlorosulfonium 1 to model alkenes was initiated to determine both the general nature of the reaction and solvent sensitivity. The results of four model reactions carried out under essentially the same conditions and times are shown in Table I. It is evident that 1 adds slowly to cyclohexene to yield 14 and readily with the more reactive styrene to yield 15. The reaction with 2,3-dihydrofuran gives 16 which is analogous to 3; 16 did not dehydrochlorinate under the conditions used. Due to its aromatic character, thiophene reacts with 1 by a substitution mechanism to yield the a-sulfonium 17. Chlorination appears to be competing with the addition reaction and the reaction with cyclohexene gave not only 14 but also considerable 1,2dichlorocyclohexane. Whether 1 reacts with an alkene to give the dichloro or sulfonium apparently depends upon the electron density of the double bond. It is interesting that the bromine complex"J2 of dimethyl sulfide in (9) Kruse, C. G.; Poels, E. K.; Jonkers, F. L.; van der Gen, A. J.Org. Chem. 1978.43. 3548. (10)Bosshard, H. Helu. Chim. Acta 1972, 55, 32. van der Gen, A.; Bosshard, H. Ibid. 1972, 55, 37. (11)Chow, Y. L.; Bakker, B. H.; Iwai, K. J.Chem. SOC.,Chem. Commun. 1980, 521. (12) Chow, Y. L.; Bakker, B. H. Synthesis 1982, 648.
Schmidt et al. Table I. Reaction of 1 with Model ComDounde model isolated yield, % solvent react ant product 3.5 none
CH,C1,
85 9.2
SO 2 CH,CI,
19.5 none
SO, CH,Cl,
15 none
SO 2 CH,Cl,
SO,
15
(7
picrylsulfonate
16
OsD
picrate
17
methylene chloride does not add directly to styrene but yields l-(2-bromo-l-phenylethyl)dimethylsulfonium bromide. This compound is derived by first formation of a three-membered bromonium intermediate followed by nucleophilic attack by dimethyl sulfide at the benzyl carbon. If the bromosulfonium salt added directly to the styrene, then the sulfonium group should be beta to the phenyl and analogous to 15. It is thus unlikely that the chlorosulfonium 1 reacts with styrene by a three-membered chloronium ion mechanism. The structure of 15 is supported by the proton NMR of the chloride salt and its ring-openedproducts 15% and 15Rb. The NMR of this sulfonium indicates the presence of a phenyl (Ph), THT', and a CHXYCH2Zgroup. The THT+ group could be either a or 0to the phenyl. Upon heating 15, a 70/30 mixture of two structures was obtained. The NMR spectrum indicated two SCH2 triplets, indicating that the THT ring had been opened to yield two types of S(CH2)&1 groups with different PhCHXCH2Y patterns. Neither product was 1,2-di~hloroethylbenzene,'~ whose CH and CH2 protons are at 4.8 and 3.86 ppm. Normal substituent effects for chloro and thioalkyl groups allow assignment of the 15R isomers as shown below. The original sulfonium 15 is assigned as having a 0-THT', because changing thio sulfur of 15R to sulfonium of 15 would deshield geminal protons and, to a lesser extent, vicinal protons. 8
15Ra major 15Rb minor 15
(CH) 5.15 4.00 5.48
6
(CH,) structure 3.21 PhCHClCH,S(CH,),CI 4.00 PhCH[S(CH,),Cl]CH,CI 3.96 PhCHClCH,(THT+)
The major isomer 15Ra was formed by ring-openingvia chloride attack at a ring carbon a to the sulfonium. The minor product 15Rb could be formed by chloride displacement of the THT followed by THT displacement of the benzyl chlorine. The resulting intermediate would then decompose by chloride ring-opening to yield 15Rb. A more probable mechanism for 15Rb is the displacement of the benzyl chlorine of 15Ra by the neighboring sulfur followed by chloride attack on the resulting three-membered sulfonium intermediate. Table I illustrates the dramatic effect the solvent has on the reactivity of 1 to alkenes. Sulfur dioxide appears (13)Heeschen, J. P.,unpublished results.
J. Org. Chem., Vol. 50, No 16, 1985 2843
Chlorine Complex of 'I'etrahydrothiophene Table 11. Proton NMR Chemical Shifts"of THT and 1-Substituted THT Rings structure solvent 6 (4 6 (PI A6 THT CCl, 2.73 1.90 0.83 DzO/HCl 2.78 1.91 0.87 sop 2.64 1.85 0.79 T H T + 0.4HCI SOZ, -20 "C 2.72 1.90 0.82 THT + 0.5SOpC1, SOZ, -20 "C 3.45 2.27 1.18 T H T + 1.2S09Clp SOZ, -20 "C 4.20 2.66 1.54 1 (ref 9) CDCI,, -75 "C 4.20 2.70 1.50 2.70 2.13 0.57 THTO CCI, 0.80 3.00 2.20 D20 1.01 3.31 2.30 DZO-HCI THT+ rings in 2, 3, DpO or Me2S0 3.6-3.8 2.2-2.45 1.3-1.4 16, 17
ppm/Me4Si. Internal chemical shift reference is Me*Si in CC14 and MezSO solution, DSS, or TSP in D,O solution. The chemical shifts given for THTO and THT' are average values, since geminal protons are not equivalent in those moieties.
to increase the reactivity to both addition and substitution reactions above that which would be expected due only to solvent polarity. This is consistent with our observed increase in reactivity of 1 in SOz with phenols4 and the increased rate of formation of 2 in SOz. We observed that the rate of decomposition of the chlorosulfonium salt 1 was greatly decreased by the presence of HC1. Hydrogen chloride decreased the amount of isolated 3 and 2, after decomposition of 1 in either The usual CH2C12or SO2,by factors of between 5 and dark Pummerer tars were minimal. The addition of HC1 during the preparation of zwitterions decreased the amount of 2 by factors of between 100 and loot) and also increased the yield of desired products4 It is probable that HC1 inhibits proton removal from 1 and interferes with the formation of the sulfocarbonium ion 12. Proton NMR. The ktrahydrothiophenium ring, THT', is a key feature of the new structures reported here, and it is important to distinguish this moiety from THT, 1, and THTO, which have pot.entially similar NMR patterns and which may occur in the various reaction mixtures examined. Table I1 presents the chemical shifts and shift differences of the a and @ protons of THT, THTO, THT+, and 1 in pertinent solvents. All CY protons of T H T and 1 have the same chemical shift and the p protons also have the same shift, due to rapid inversion or planar shape of the ring. For THTO and THT+, geminal protons are nonequivalent due to the single additional substituent on the pyramidal, noninverting sulfur, and Table I1 reports the average a and proton shifts. The chemical shifts of T H T are essentially the same in CC14,aqueous acid, SOz, and SO2 with HC1, and the shift difference ranges from 0.79 to 0.87 ppm. This small range implies little or no interaction of THT with these solvents or HCl. Chlorine forms complexes preferentially with T H T to make 1 and exchanges rapidly among all T H T molecules at temperatures down to -20 "C. The exchange is reported7 to be slow for 1 in CDC1, at -75 OC. In the presence o f 1.2 mol of chlorine, as S02C12,1 displays a single spectrum with the same shifts as have been reported for the nonexchanging structure in CDC13solvent. When only 0.5 mol of chlorine is available, a single time-averaged T H T spectrum is observed that shows a rapid exchange of C12among all T H T molecules, and the shift is halfway between that for zero and full complexation. This demonstratev that the Clz association must be almost entirely with T H T and not with SO2. Tetrahydrothiophene 1-oxide ('1'H'T'O) displays non-
equivalence of geminal protons, resulting in a pattern of the type AA'BB'MM'NN', with obvious broadening or separation of the a proton absorptions. In contrast to THT, THTO displays a very noticeable solvent effect on chemical shift, going from CCll to water to aqueous acid. The tetrahydrothiophenium ring, THT+, also has an AA'BB'MM'NN' pattern, but not identical with THTO. It appears as complex absorptions of equal area centered at 3.6-3.8 ppm and at 2.2-2.4 ppm. At 60 MHz each region usually has a single maximum and the width varies from 15 Hz (as for T H T itself) to 30 Hz. A t high resonance frequency, each region usually splits into two complex patterns of equal area. This behavior is characteristic of THT+ and THTO. The average chemical shift difference between a and p protons is remarkably constant, at 1.3 to 1.4 ppm, despite the strong solvent effects on their absolute values. Table 111 summarizes distinctive proton NMR features of the substituted THT rings, including the chemical shifts of protons at the substitution sites and coupling between them. The positions of substituents C1, THT', and OH on THT rings have been established with good confidence, on the basis of authentic fabrication and/or NMR chemical shift substituent effects and detection of vicinal coupling. In almost all cases the presence of both the cis and trans isomers of a given 2,3-disubstituted structure was supported on the basis that the coupled H(2) and H(3) proton signals appeared in major/minor sets with similar chemical shifts and constant molar ratios of the order of about 5:l. It is possible to assign configurations and conformations to 3 , 4 , 5 , and 6 by examining the NMR spin-spin coupling constants between vicinal protons on the substituted THT ring. The three-bond coupling between vicinal protons, J(H-C-C-H), is dependent on the dihedral angle between the individual C-H bonds due to rotation about the intervening C-C bond. For tetrahedral carbons a reasonable description of both magnitude and angular dependence is given by the modified KarplusI4 relation, J(vic) = 7 - cos 4 5 cos 24 Hz. Substituents which are strongly electron-withdrawing may reduce the magnitude but not the general angular dependence. Ring inversion is fast on the NMR time scale, so a single time-averaged spectrum is observed. Observed splittings (Experimental Section) were used for this analysis because they are sufficiently close to the true coupling constants to be diagnostic. The major isomer of 2,3-diCl-THT (6), is assigned as having the chlorine atoms trans and fixed diaxial in a half-chair conformation of the ring. Rotation about all of the C-C bonds is approximately 30" from a planar (eclipsed) conformation. The J(23) value of 1.2 Hz establishes that H(2) and H(3) are 70-110' apart and therefore trans-diequatorial. Protons H(3), H'(4) at 6 2.41, and H(5) a t fi 3.23 also are equatorial with respect to their vicinal CH2 protons, on the basis of individual and summed couplings, and H(4) and H'(5) are axial. The relatively large four-bond coupling of 1.2 Hz between H(2) and the equatorial H'(4) supports the implied planar "W" H-CC -C-H path between them. This demonstration of trans configuration and diaxial conformation of the major 2,3diC1-THT isomer confirms the same assertion by others7x9 on the basis of J(2,3) alone. The minor isomer of 6 must be cis-2,3-diCl-THT. The C(2) chlorine is axial, the C(3) chlorine is equatorial, and the ring is puckered. Vicinal couplings indicate that H(2) and H(3) are cis axial-equatorial. Proton H(3) is most
+
(14) Recker, E. D."High Resolution NMR", 2nd ed.; Academic Press: Philndelphia, PA, 1979; p 657.
2844 J . Org. Chem., Vol. 50, No. 16, 1985
Schmidt et al.
Table 111. Proton NMR Description of 2,3-Disubstituted Tetrahydrothiophenes and Related Structures substit bH(2) 6H(3),ppm 5(2,3),Hz solvent, remarks structure 2 3 tetrahydrothiophene: 5.68 2.49 1.5 5 c1 H 2.18 4.5 CCl* 5.55 ?
